Abstract

Background

Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is an extremely rare autosomal recessive disorder. In addition to the juxtacentromeric heterochromatic instability, the disease is characterized by variable reduction in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood as well as exhibit facial dysmorphism including hypertelorism, epicanthal folds, and low-set ears.

Subjects and Methods

A case series of five patients with ICF from a major immunodeficiency center in Saudi Arabia were included. Immunological and cytogenetic studies were performed for all the five patients. Molecular data was conducted on three patients.

Results

All patients had variable hypogammaglobulinemia and characteristic centromeric instability of chromosomes 1, 16, and sometimes 9. One of the patients had pseudomonas meningitis. Pauciarticular arthritis was noted in one patient, a previously not reported finding in ICF, though it has been reported among patients with humoral immune defect. In addition, we identified a novel homozygous c.2506 G>A (p.V836M) mutation in DNMT3B in one of the three patients tested.

Conclusions

This report describes five patients with ICF Saudi Arabia for the first time. ICF should be suspected in children with facial dysmorphism who present with recurrent infections especially in highly inbred populations.